Revised: July 27, 2013
Accepted: August 20, 2013
Published online: September 28, 2013
Processing time: 105 Days and 15 Hours
We hypothesize that susceptibility to post-traumatic stress disorder (PTSD) may be determined in part by aberrant microtubule-associated protein tau expression in neurons of critical brain structures. The following lines of evidence support this hypothesis. First, epidemiologic data suggest the involvement of genetic factors in the susceptibility to PTSD. Second, the common features of both abnormal tau expression and PTSD include amygdalar and hippocampal atrophy, upregulation of norepinephrine biosynthetic capacity in the surviving locus coeruleus neurons and dysfunction of N-methyl-D-aspartate-receptors. Finally, our experiments using rTg4510 mice, a model that over-expresses human mutant tau and develops age-dependent tauopathy, demonstrate that these animals display circling behavior thought to be related to states of anxiety. To detect the potential molecular mechanisms underlying PTSD episodes, laser-assisted/capture microdissection can be used with microarray analysis as an alternative approach to identify changes in gene expression in excitatory and/or inhibitory neurons in critical brain structures (i.e., hippocampus and amygdala) in response to the onset of PTSD.
Core tip: We propose that susceptibility to post-traumatic stress disorder (PTSD) may be determined, in part, by aberrant microtubule-associated protein tau expression in neurons of critical brain structures. We review several lines of evidence to support this novel hypothesis. In addition, we review types of PTSD, namely non-classical PTSD, induced by various medical conditions and address this issue of why non-classical PTSD can be reliably elicited. To verify our hypothesis, we propose to use animal models of PTSD combined with laser-assisted/capture microdissection and microarray analysis to examine gene expression changes in selected cellular elements in response to the occurrence of PTSD.